Abstract
We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. Saline or fecal suspensions with a standardized dose range of bacterial colony-forming units (CFUs) were injected intraperitoneally into Sprague–Dawley rats. The qualitative composition of the initial inoculum and the ascites was analyzed separately by MALDI-TOF mass spectrometry. Invasive monitoring was conducted in separate anesthetized groups (n = 12–13/group) after 12, 24, 48 and 72 h to determine rat-specific organ failure assessment (ROFA) scores. Death and ROFA scores peaked at 24 h. At this time, 20% mortality occurred in animals receiving a monomicrobial E. coli suspension, and ROFA scores were significantly higher in the monomicrobial subgroup than in the polymicrobial one (median 6.5; 5.0–7.0 and 5.0; 4.75–5.0, respectively). ROFA scores dropped after 48 h, accompanied by a steady decrease in ascites CFUs and a shift towards intra-abdominal monomicrobial E. coli cultures. Furthermore, we found a relationship between ascites CFUs and the evolving change in ROFA scores throughout the study. Hence, quantitatively identical bacterial loads with mono- or polymicrobial dominance lead to a different degree of sepsis severity and divergent outcomes. Initial and intraperitoneal microbiological testing should be used to improve translational research success.
Highlights
We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents
We have used a qualitative, murinespecific sickness scoring system, and we have developed a comprehensive, Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS)-compatible evaluation of organ function parameters to adequately quantify the clinical condition of the septic animals with a rat-specific organ failure assessment (ROFA) scoring s ystem[9] between 12 and 72 h after induction
Intra-abdominal sepsis was induced by fecal inoculum with known colony forming units (CFUs)
Summary
We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. The question of whether a dominant strain or certain strains collectively—a single component or a multicultural microbial community—will determine the initial severity and the natural course of bacterial sepsis remains unresolved Based on this knowledge gap, we hypothesized that the unknown qualitative bacterial composition within the fecal mass triggering the insults could be a highly important confounding factor and a decisive descriptor of the course of a septic scenario. Progressively evolving experimental sepsis as a function of time To this end, we have used a qualitative, murinespecific sickness scoring system, and we have developed a comprehensive, MQTiPSS-compatible evaluation of organ function parameters to adequately quantify the clinical condition of the septic animals with a rat-specific organ failure assessment (ROFA) scoring s ystem[9] between 12 and 72 h after induction
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